T cell receptor usage of virus-specific CD8 cells and recognition of viralmutations during acute and persistent hepatitis B virus infection

T cells specific for a single viral epitope, but using different T cell rec eptors, should have flexibility in their epitope recognition to protect the infected host against the emergence of viral escape mutants. Therefore, po lyclonality of the hepatitis B virus (HBV)-specific cytotoxic T lymphocyte response has been hypothesized to be a major determinant in the control of infection. We analyzed the V beta chain composition of the core 18-27-speci fic GD8 cells in acute and persistently HBV-infected patients using HLA-A2 tetrameric complexes and a panel of V beta antibodies. Different T cell rec eptors were utilized by core 18-27-specific CD8 cells both in patients with acute and chronic infection. The functional ability of these epitope-speci fic T cells to respond to potential viral mutations was then tested. The po lyclonal HBV-specific CD8 response present in patients with acute hepatitis displayed a limited efficiency to recognize mutations introduced within th e epitope. The ability of core 18-27-specific CD8 to tolerate epitope mutat ions was found only during persistent HBV infection. The data suggest that although a clonally heterogeneous CD8 response can be largely inhibited by the occurrence of single epitope mutations in primary HBV infection, prefer ential selection of T cells able to counteract the emergence of viral mutat ions can occur during persistent infection.